Total joint arthroplasty following intra-articular steroid injection : A literature review

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1 Acta Orthop. Belg., 2013, 79, REVIEW ARTICLE Total joint arthroplasty following intra-articular steroid injection : A literature review Samuel E. McMahon, Johannes A. Leroux, Toby O. Smith, Caroline B. Hing Department of Trauma and Orthopaedics, Frere Hospital, East London, Eastern Cape, South Africa This study aimed to identify, by systematic review of the literature, whether intra-articular steroid injection before total joint replacement confers an increased risk of post-operative deep prosthetic. All studies assessing the incidence of deep prosthetic in patients who had undergone steroid injection in the same joint were included. A mixed metaanalysis and narrative review of 12 studies with 2068 participants was conducted. Steroid injection prior to total joint replacement was found to confer no increased risk of deep or superficial prosthetic (CI = 95%). We found no evidence of a link between injection and deep joint, and conclude that this is a safe procedure when conducted with aseptic precautions. We suggest a prospective randomised control trial to provide conclusive data on this question. Keywords : steroid ; injection ; knee ; hip ; ; joint replacement ; arthroplasty. INTRODUCTION Osteoarthritis (OA) affects 8.5 million people in the UK (3), and causes a significant economic burden, with 850 million spent on total joint replacement, and a loss of economic production of 3.2 billion in 2012 (6). The management of OA ranges from conservative measures (analgesia, physiotherapy, intra- articular steroid injection (IASI) to surgical intervention (mostly joint replacement). Intra-articular steroid injection has been used as a symptomatic treatment for OA for half a century (25), and is known to be effective for short term (up to 24 weeks) relief of symptoms in both knee (2) and hip (28) OA. When combined with local anaesthetic it can be used to distinguish true hip pain from referred spinal pain prior to further invasive n Samuel E. McMahon, MBChB BSc(Hons) MRCS, Orthopaedic Officer. Department of Trauma and Orthopaedics, Frere Hospital, East London, Eastern Cape, South Africa. n Johannes A. LeRoux, MBChB(stell) DA(SA), Orthopaedic Officer. Department of Trauma and Orthopaedics, Frere Hospital, East London, Eastern Cape, South Africa. n Toby O. Smith, PhD MSc MCSP, University Lecturer. Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK. n Caroline B. Hing, MSc MD FRCS(Tr&Orth), Honorary Senior Lecturer & Consultant Orthopaedic Surgeon. Department of Trauma and Orthopaedics, St George s University London, Tooting, London, UK. Correspondence : Mr S. McMahon, Department of Trauma and Orthopaedics, Frere Hospital, Amalinda Drive, East London, Eastern Cape, 5201 South Africa. sammc84@gmail.com 2013, Acta Orthopædica Belgica. No benefits or funds were received in support of this study. The authors report no conflict of interests.

2 total joint arthroplasty following intra-articular steroid injection 673 treatment (18). The American College of Rheumatologists have advocated intra-articular steroid injections in their latest guidelines when a patient does not respond to simple analgesia, although there are no recommendations on the number or frequency of injections (13). Intra-articular steroid injection is, however, not without risk and a number of complications have been reported including septic arthritis (5), tendon rupture (36) and articular cartilage degeneration experimentally (4). Therefore, the decision to administer an IASI should not be taken lightly. There has been debate in the literature as to whether IASI prior to total joint replacement, both of the hip and the knee, causes an increased risk of deep joint following surgery. This study aims to review the current literature regarding this question. Eligibility MATERIALS AND METHODS We included all studies assessing the incidence of following total joint replacement in patients who had undergone IASI in the same joint. Only studies assessing clinical outcomes of human subjects were included. All potentially eligible studies were included irrespective of study design, language of publication or method/risk of bias. Search strategy We performed a PRISMA compliant (26) search to identify relevant articles from 1985 to September 2012 using online literature databases. Study identification The title and abstract of each study were reviewed. Full text papers were ordered of those studies pertinent to the research question and these were reviewed against the eligibility criteria. Critical appraisal The critical appraisal was conducted using a modified version of the Critical Appraisal Skills Programme (CASP) (15) tools for case-control and cohort studies. Data analysis A meta-analysis was undertaken where there was limited between-study heterogeneity in respect to cohort characteristics, study design, intervention and follow-up assessments. When there was between-study heterogeneity, a narrative synthesis of the study findings was undertaken. When pooled analysis was deemed appropriate, statistical heterogeneity was evaluated using the inconsistency value (I 2 ) and Chi-squared tests. In instances where I 2 was below 20% and Chi-squared reported p- values of above 0.01, a fixed-effects meta-analysis was undertaken. When these were not satisfied, a random-effects model was utilised. The primary analysis questions were to investigate the difference in incidence between individuals who received an intra-articular injection (hip or knee) and subsequent deep joint or superficial wound post- total hip replacement (THR) or total knee replacement (TKR) respectively. Accordingly odds ratio (OR) analyses were undertaken, with data reported as a ratio and with 95% confidence interval (CI) and p-value data. All meta-analyses were undertaken on RevMan (Review Manager) [Computer program]. Version 5.1. Copenhagen : The Nordic Cochrane Centre, The Cochrane Collaboration, 2011). Search Results RESULTS Twelve studies from 252 initial studies were included for review. Eight studies investigated the effect of IASI and THR (7,17,20,22,23,24,33,34), 4 for IASI and TKR (9,14,16,29). Critical Appraisal The CASP (15) appraisal showed that the studies were generally of a high standard. They all had clearly defined aims, and were structured and conducted appropriately to meet them. The results were precise and able to be applied to the local population. All of the case-control studies took into account confounding factors when matching their cohorts, apart from Papavasiliou et al (29) where no matching was performed.

3 674 s. e. mcmahon, j. a. leroux, t. o. smith, c. b. hing Study Study Design Study/ Group Chitre et al 2007 Karuppiah et al 2007 Kaspar et al 2005 McIntosh et al 2006 McMahon et al 2012 Meermans et al 2012 Sankar et al 2012 Sreekumar et al 2007 Retrospective analysis Retrospective analysis Table I. Cohort Characteristics IASI in THR Gender Age (years) (M/F) No of cases IASI to THR interval (months) Follow-up (months) Deep Superficial Study 36 NR 63.7 (30-83) 18 (4-50) 25.8 (9-78) 0 1 Study /76 NR Case control Study 40 25/ (45-87) ( ) 33.2 ( ) 4 N/A (46-87) 30.2 ( ) 0 N/A Case Study / (35-94) 3.7 (SD 2.7) 32.4 (SD 16.8) (41-92) 31.2 (SD 19.2) 1 8 Prospective Study 49 N/R 69.0 (51-98) 12.1 (SD 5.1) 97.8 (85-117) 1 1 analysis Case Study / ) (12-131) / (18-85) 70.5 (15-129) 1 7 Retrospective Study 40 10/ (52-83) 6.2 (2-23) 23.2 (11-37) 0 1 review Case Study 68 15/ (32-89) / (39-89) F female ; IASI - Intra-Articular Steroid Injection ; M Male ; NR not reported ; THR Total Hip Replacement. Cohort Characteristics A summary of the cohort characteristics is available in Table I (THR) and Table II (TKR). For the THR studies, a total of 1342 participants were reviewed. Two studies did not state the gender mix of their cohorts (7,23) ; the other studies included 290 males and 659 females. The mean age of the cohorts ranged from 62.2 years (34) to 75.0 years (20). Follow-up periods ranged from 22.3 months (34) to 97.8 months (23). For the TKR studies, a total of 726 participants were reviewed. Gender mix and mean ages were not reported in two studies (14,29). The other studies included 127 males and 187 females. Mean ages ranged from 68 years (9) to 72 years (9). Follow-up periods ranged from 33 months (9) to 79 months (16). Clinical Findings THR deep : Four case-control studies (n = 1087) were pooled in this analysis (Kaspar et al (20) ; McIntosh et al (22) ; Meermans et al (24) ; Sreekumar et al (34)). The odds ratio indicated individuals were twice as likely to develop a deep if they received an intra-articular steroid injection prior to THR compared to no injection, but this was not statistically significant (p = 0.12) and therefore may be considered a chance result. The pooled odd ratio was 2.65 (95%CI : 0.79, 8.96 ; Fig. 1). THR superficial : Three case-control studies (n = 1007) were pooled for this analysis (22,24,34)). The meta-analysis indicated no difference in the incidence of superficial between those who received an intra-articular steroid injection prior to THR compared to no injection (OR : 1.04 ; 95% CI : 0.52, 2.10 ; Fig. 2). The low incidences of superficial and deep s are re-iterated across the retrospective cohort dataset. Chitre et al (7), McMahon et al (23), Sankar et al (33) and Karrupiah et al (17) all reported acceptable deep rates. TKA deep : Two case-control studies (n = 414) were pooled in this analysis (Desai et al (9) ; Papavasiliou et al (29)). Whilst the odds ratio

4 total joint arthroplasty following intra-articular steroid injection 675 Study Desai et al 2008 Horne et al 2008 Joshy et al 2006 Papavasiliou et al 2006 Study Design Case Case Case Case Study/ Group No of cases Table II. Cohort Characteristics IASI in TKR Gender (M/F) Age (years) IASI to TKR interval (months) Follow-up (months) Deep Superficial Unspecified Study 90 26/54 68 (49-87) NR 33 (12-72) 0 2 NR /96 72 (51-88) 48 (12-72) 0 5 NR Study 29 NR NR 16 (1-540) NR NR NR NR NR NR NR NR 0 Study 32 14/18 69 (46-86) 46 (12-121) 79 (22-170) 32 0 NR 32 13/19 70 (47-86) 59 (13-132) 77 (23-156) Study 54 NR NR NR NR 3 12 NR 90 NR NR 0 10 NR F female ; IASI Intra-Articular Steroid Injection ; M Male ; NR not reported ; TKR Total Knee Replacement. Chi 2 ; Chi-Squared test, I 2 ; inconsistency test, Z ; Z-Score, M-H ; Mantel-Haenszel Test, CI ; Confidence Interval. Fig. 1. Forest plot reporting the incidence of THR deep between those who received an intra-articular steroid injection prior to THR compared to no injection. indicated people were twice as likely to develop a deep if they received an intra-articular steroid injection prior to TKR compared to no injection, this was not statistically significant (p = 0.64) ; and may be considered a chance result. The pooled odd ratio was 2.24 (95% CI : 0.08, ; Fig. 3). TKR superficial : Two case-control studies (n = 414) were pooled in this analysis (Desai et al (9) ; Papavasiliou et al (29)). The meta-analysis indicated no difference in the incidence of superficial between those who received an intraarticular steroid injection prior to TKA compared to no injection (OR : 0.91 ; 95% CI : 0.07, ; Fig. 4). TKR unspecified : Two case-control studies (n = 312) were pooled in this analysis for reported not specifying whether this was deep or superficial (Horne et al (14) ; Joshy et al (16)). The meta-analysis showed no difference in the incidence of IASI prior to operation in TKRs that went on to become infected and those that did not (OR : 1.12 ; 95% CI : 0.56, 2.25 ; Fig. 5). Joshy et al (16) specified that their study cohort was comprised of patients with proven deep joint, whereas Horne et al (14) included patients who had had a readmission with wound healing problems and a suspected within six months of TKR or who, at any stage, had revision knee surgery for an infected joint. On narrative

5 676 s. e. mcmahon, j. a. leroux, t. o. smith, c. b. hing Fig. 2. Forest plot reporting the incidence of THR superficial between those who received an intra-articular steroid injection prior to THR compared to no injection. Fig. 3. Forest plot reporting the incidence of TKA deep between those who received an intra-articular steroid injection prior to TKA compared to no injection. Fig. 4. Forest plot reporting the incidence of TKA superficial between those who received an intra-articular steroid injection prior to TKA compared to no injection. review, no relationship between IASI and deep or superficial was identified by Horne et al (14) or Joshy et al (16). DISCUSSION Deep joint following arthroplasty is a catastrophic event. The incidence is increasing and diagnosis can be challenging (30). Revision surgery following is associated with longer opera- tive time, more blood loss, and a higher number of complications compared with revisions for aseptic loosening or primary THR, and the mean cost of revision surgery in cases of sepsis was found to be 21,937 compared 11,897 in aseptic cases in the UK (37). There is experimental evidence that prior IASI leads to an increased risk (1,11). However, there are a number of factors known to impact risk within an individual patient (12,21,31, 32,35).

6 total joint arthroplasty following intra-articular steroid injection 677 Fig. 5. Forest plot reporting the incidence of TKA unspecified between those who received an intra-articular steroid injection prior to TKA compared to no injection. Concern regarding the effect of IASI on rates in subsequent THR was first raised by Kaspar and de Beer (18,29). Their study published in 2006 (20) found a 10% rate in patients who had received an IASI prior to THR. This result appears to have since been refuted by the subsequent studies conducted. It was initially suggested by McIntosh et al (22) that a short interval between IASI and THR may have had an effect. However, this appears not to be the case as Sankar et al (33) conducted their study with a mean interval of 6.2 months (2-23) without adverse effect. The setting of the IASI may be significant. Kaspar et al (20) report conducting IASIs in a fluoroscopy suite. They describe adequate skin preparation and aseptic technique, however it is not described what the ambient conditions in the suite were, and it has been suggested that pathogenic organisms may be introduced in to the joint at that time. McIntosh et al (22) also described the IASI being done by members of the radiology department, although it is not specified whether this was in the radiology department or theatres. They found a non-significant increase in deep rate (1.3% vs. 0.45%) although both rates were within the historic rate reported at the study institution between 1969 and Subsequent studies have all described the sterility of the environment and procedure undertaken. Papavasiliou et al (29) identified a significant increase in deep prosthetic following TKR in patients who had undergone IASI. The study did not find any significance in the timing or number of injections. Interestingly, Papavasiliou et al (29) did not match their control cohort. The control was taken as the consecutive patients within the series who did not receive IASI prior to TKR. Most IASIs to the knee are conducted in a clinic setting with only a cursory attempt at aseptic technique. Desai et al (9) conducted injections in the operating theatre with strict aseptic procedures observed, and recorded no deep s in their series. Horne et al (14) conducted an interesting retrospective study. Several different health professionals had conducted the IASI (general practitioners, orthopaedic surgeons and rheumatologists), and it can be assumed that the injections were therefore conducted under varying degrees of asepsis, No increased risk of developing postoperative wound problems or deep prosthetic s was identified. In view of evidence that both smoking (10) and diabetes (27) increase the risk of wound complications, no increase was detected by Horne et al (14) although it is suspected that the number of patients admitting to smoking was underreported. We believe that the current evidence suggests that IASI prior to total joint replacement is safe, when conducted within appropriate aseptic conditions. The documented symptomatic benefits experienced by patients outweigh the small risk of immediate complications, and the large majority of studies show it confers no increased risk of joint sepsis. Our conclusions must be viewed with some caution as they are based on level II evidence. A randomised control trial would provide conclusive evidence with regards to the study question, however we accept that this would be difficult to undertake due to the invasive nature of an IASI.

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